Mice continuously exposed to nitrous oxide, 50 per cent, for two to three weeks become tolerant to anesthesia, as evidenced by an increase in the concentration of nitrous oxide necessary to abolish the righting reflex from 1.49 ± 0.045 atm to 1.67 ± 0.053 atm after three weeks (auto-tolerance). Also, there was an increase in the concentration of a second anesthetic (cyclopropane or isoflurane) necessary to abolish the righting reflex (cross-tolerance). Cyclopropane ED50 increased from 0.130 ± 0.0068 atm to 0.148 ± 0.0044 atm after two weeks of exposure to nitrous oxide, 50 per cent. Isoflurane ED50 increased from 0.00570 ± 0.000163 atm to 0.00622 ± 0.000200 atm after three weeks of exposure to nitrous oxide, 50 per cent. Mice continuously exposed to isoflurane, 0.15 or 0.3 per cent, manifested neither auto- nor cross-tolerance. After three weeks of exposure, 69 per cent of mice removed from nitrous oxide, 50 per cent, convulsed when gently suspended by the tail (i.e., manifested a stimulus-elicited withdrawal syndrome indicating dependence on nitrous oxide). After three weeks of exposure, 43 per cent of mice convulsed when removed from isoflurane, 0.15 per cent. However, only 4 per cent of mice convulsed after six or nine weeks of exposure to this concentration of isoflurane.